Morphometric characterization of brain arteriovenous malformations for clinical and radiological studies to identify silent intralesional microhemorrhages.

Clinical Neuropathology, Vol. 35 – No. 3/2016 (114-121) Morphometric characterization of brain arteriovenous malformations for clinical and radiological studies to identify silent intralesional microhemorrhages ©2016 Dustri-Verlag Dr. K. Feistle ISSN 0722-5091 DOI 10.5414/NP300937 e-pub: April 6, 2016 Melike Pekmezci 1 , Jeffrey Nelson 2,3 , Hua Su 2,3 , Christopher Hess 4 , Michael T. Lawton 2,4 , Melda Sonmez 1 , William L. Young 2,3,5† , Helen Kim 2,3 , and Tarik Tihan 1 of Pathology, 2 Center for Cerebrovascular Research, 3 Department of Anesthesiology, 4 Department of Radiology and Biomedical Imaging, and 5 Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA 1 Department Key words arteriovenous malforma- tion – AVM – cerebro- vascular disease – hemorrhage – silent intralesional microhem- orrhage – stroke Deceased. Received December 28, 2015; accepted in revised form February 15, 2016 Correspondence to Melike Pekmezci, MD University of California, San Francisco, Department of Pathol- ogy, Neuropathology Division, Room M551, 505 Parnassus Avenue, San Francisco, CA 94143-0102, USA melike.pekmezci@ ucsf.edu Abstract. Brain arteriovenous malfor- mations (bAVMs) are vascular lesions that can cause significant morbidity and mortali- ty, particularly when they bleed, i.e., rupture. Determining the risk of rupture for bAVMs is a crucial task to determine the most ap- propriate approach to patients with bAVM. Furthermore, patients who present with a hemorrhagic event also have a higher risk of subsequent hemorrhage. Determination of the hemorrhage risk and management strat- egy for incidentally discovered bAVMs still remains a controversial subject. In recent years, we have identified silent intralesional microhemorrhages (SIMs) as a possible risk factor for subsequent hemorrhage in patients with bAVMs. The principal aim of this study was to determine critical histological fea- tures that can be correlated with preopera- tive radioimaging findings, and allow better identification of patients with greater risk of adverse outcome. Here we provide a detailed descriptive analysis of the morphometric assessment of bAVMs in order to provide reproducible methodology that will aid in correlating preoperative radioimaging find- ings with histological features that may be significantly associated with increased risk of hemorrhage/rupture. Introduction Brain arteriovenous malformations (bAVMs) are considered to be congenital defects of cerebrovascular tree that can be found anywhere, but are most common in the supratentorial region [1, 2]. The original ob- servations highlighted “arterialized” vessels with disrupted elastic lamina, marked vascu- lar mural collagenization, focal proliferation of the smooth muscle layer of the arteries, and inflammatory cells such as macrophages and lymphocytes [3, 4, 5, 6]. Interposed pa- renchyma contains occasional reactive glial cells, and rarely, hemosiderin pigment. In some cases, no reactive changes are seen. The core of the bAVMs is characterized by a tangle of abnormal arteries and veins, and referred to as the nidus, which has been diffi- cult to ascertain in histology without surgical correlation. While many AVMs have mac- rophages and marginating neutrophils, oc- casional lesions harbor significant amounts of parenchymal or perivascular lymphocytic infiltrates [7]. The prevalence and clinical significance of the above-mentioned mor- phological features of bAVMs have not been well documented. The most common symptoms associ- ated with bAVMs are headaches, seizures, or symptoms associated with intracranial hem- orrhage. In recent years, “unruptured” AVMs are increasingly being detected in clinical practice in patients who have no associated symptoms, during imaging for unrelated rea- sons [8]. One of the most critical issues in bAVMs is the possibility of hemorrhage, and this poses a significant morbidity given that nearly half of the bAVMs present initially with a hemorrhagic picture [9, 10, 11]. The annual hemorrhage rate of bAVMs is report- ed to be ~ 2 – 4% [12, 13]. In addition, bAVM patients who present with intracranial hem- orrhage also have a higher risk of subsequent bleeding [11, 12, 14]. A number of grading